Easy and Stereoselective Synthesis of Cyclopropyl-Substituted Phosphonates via α-Chlorophosphonates

Abstract

A facile stereoselective synthesis of cyclopropylphosphonates from the reaction of inexpensive α-chlorophosphonates with alkyl acrylates in the presence of sodium hydride is reported. Reaction with dimethyl maleate or fumarate also leads to cyclopropyl-substituted phosphonates. These reactions take place via Michael addition of acrylate, dimethyl maleate, or fumarate to the phosphonate carbanion, followed by expulsion of the chloride ion.

Key words

phosphonates - Michael addition - acrylates - diastereo­mers - cyclopropanes

References

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8

We have utilized the reaction of inexpensive PBr₃ with α-hydroxyphosphonates also to prepare a series of 2-[aryl(bromo)methyl]-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxides (aryl = phenyl, 4-methylphenyl, 4-chlorophenyl, 4-bromophenyl); some of these compound have been previously reported. [²a] Note that 2-(1-hydroxy-3-phenyl-prop-2-enyl)-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxide affords two types of cinnamyl-substituted bromophos­-phonates 2-(1-bromo-3-phenylprop-2-enyl)-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxide and 2-(3-bromo-3-phenyl-prop-1-enyl)-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxide, while the using 2-[hydroxy(2-furyl)methyl]-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxide affords 2-(5-bromo-2-furyl)-5,5-dimethyl-1,3,2-dioxaphosphinane 1-oxide. More details are available from the authors or in ref. 9.

10

All data has been deposited at the Cambridge database. We believe that such information will be useful, in case these compounds are pharmacologically active.